Department of Physiology, AZCOM, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA.
Department of Genetics & Genome Sciences & Department of Pediatrics, Case Western Reserve University, 10900 Euclid Avenue, 830 BRB, Cleveland, OH 44106, USA.
Nutrients. 2018 Oct 3;10(10):1418. doi: 10.3390/nu10101418.
Genistein is a naturally occurring isoflavone found in soy. Genistein has been shown to increase the open probability of the most common cystic fibrosis (CF) disease-associated mutation, ∆F508-CFTR. Mice homozygous for the ∆F508 mutation are characterized with severe intestinal disease and require constant laxative treatment for survival. This pathology mimics the intestinal obstruction (meconium ileus) seen in some cystic fibrosis patients. This study tested whether dietary supplementation with genistein would reduce the dependence of the ∆F508 CF mouse model on laxatives for survival, thereby improving mortality rates. At weaning (21 days), homozygous ∆F508 mice were maintained on one of three diet regimens for a period of up to 65 days: normal diet, normal diet plus colyte, or genistein diet. Survival rates for males were as follows: standard diet (38%, = 21), standard diet plus colyte (83%, = 42) and genistein diet (60%, = 15). Survival rates for females were as follows: standard diet (47%, = 19), standard diet plus colyte (71%, = 38), and genistein diet (87%, = 15). Average weight of male mice fed genistein diet increased by ~2.5 g more ( = 0.006) compared to those with colyte treatment. Genistein diet did not change final body weight of females. Expression of intestinal SGLT-1 increased 2-fold ( = 0.0005) with genistein diet in females (no change in males, = 0.722). Expression of GLUT2 and GLUT5 was comparable between all diet groups. Genistein diet reduced the number of goblet cells per micrometer of crypt depth in female ( = 0.0483), yet was without effect in males ( = 0.7267). The results from this study demonstrate that supplementation of diet with genistein for ~45 days increases the survival rate of female ∆F508-CF mice (precluding the requirement for laxatives), and genistein only improves weight gain in males.
染料木黄酮是一种天然存在的异黄酮，存在于大豆中。研究表明，染料木黄酮可增加最常见的囊性纤维化（CF）相关突变体 ∆F508-CFTR 的开放概率。纯合子携带 ∆F508 突变的小鼠表现出严重的肠道疾病，需要持续使用泻药才能存活。这种病理类似于某些囊性纤维化患者的肠梗阻（胎粪性肠梗阻）。本研究测试了膳食补充染料木黄酮是否会减少 ∆F508 CF 小鼠模型对生存所需泻药的依赖，从而提高死亡率。在断奶（21 天）时，纯合子 ∆F508 小鼠被维持在三种饮食方案之一中，为期长达 65 天：正常饮食、正常饮食加 colyte 或染料木黄酮饮食。雄性的存活率如下：标准饮食（38%， = 21），标准饮食加 colyte（83%， = 42）和染料木黄酮饮食（60%， = 15）。雌性的存活率如下：标准饮食（47%， = 19），标准饮食加 colyte（71%， = 38）和染料木黄酮饮食（87%， = 15）。喂食染料木黄酮饮食的雄性小鼠的平均体重增加了约 2.5 克（ = 0.006），而 colyte 治疗组则没有变化。染料木黄酮饮食没有改变雌性的最终体重。雌性的肠道 SGLT-1 表达增加了 2 倍（ = 0.0005），而雄性则没有变化（ = 0.722）。所有饮食组的 GLUT2 和 GLUT5 表达均相似。染料木黄酮饮食减少了雌性每毫米隐窝深度的杯状细胞数量（ = 0.0483），但对雄性没有影响（ = 0.7267）。本研究的结果表明，膳食补充染料木黄酮约 45 天可提高雌性 ∆F508-CF 小鼠的存活率（无需使用泻药），而染料木黄酮仅可改善雄性的体重增加。
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